PXD020139

PXD020139 is an original dataset announced via ProteomeXchange.

Title	Genetic mechanisms of cardiac sex diparities
Description	Male and female disease states differ in their prevalence, treatment responses, and survival rates. In cardiac disease, women almost uniformly fare far worse than men1-3. Though sex plays a critical role in cardiac disease, the mechanisms underlying sex differences in cardiac homeostasis and disease remain unexplained. Here, we reveal sex-specific cardiac transcriptomes and proteomes and show that cardiac sex differences are predominately controlled via post-transcriptional mechanisms. Using a quantitative proteomics-based approach, we characterize differential sex-specific enriched cardiac proteins, protein complexes, and biological sex processes in the context of global genetic diversity of the Collaborative Cross. We show that differences in cardiac protein expression are established by both hormonal and genetic mechanisms and define two additional pathways, one that is SRY dependent and one that is SRY-independent. We also determined the onset of sex-biased protein expression and discovered that sex disparities in heart tissue occur at the earliest stages of heart development, during the period preceding primary mammalian sex determination. This may explain why congenital heart disease, a leading cause of death whose origin is often developmental, is sex biased. Our results reveal the molecular foundations for the differences in cardiac tissue that underlie sex disparities in health, disease, and treatment outcomes.
HostingRepository	PRIDE
AnnounceDate	2022-08-11
AnnouncementXML	Submission_2022-08-11_14:24:19.414.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Xinlei Sheng
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: 10090;
ModificationList	phosphorylated residue; acetylated residue; iodoacetamide derivatized residue
Instrument	Q Exactive HF

Revision	Datetime	Status	ChangeLog Entry
0	2020-07-01 08:06:55	ID requested
⏵ 1	2022-08-11 14:24:20	announced

Shi W, Sheng X, Dorr KM, Hutton JE, Emerson JI, Davies HA, Andrade TD, Wasson LK, Greco TM, Hashimoto Y, Federspiel JD, Robbe ZL, Chen X, Arnold AP, Cristea IM, Conlon FL, Cardiac proteomics reveals sex chromosome-dependent differences between males and females that arise prior to gonad formation. Dev Cell, 56(21):3019-3034.e7(2021) [pubmed]

submitter keyword: mouse heart, sex disparities

Ileana M. Cristea
contact affiliation	Department of Molecular Biology, Princeton University
contact email	icristea@princeton.edu
lab head
Xinlei Sheng
contact affiliation	Princeton University
contact email	xsheng@princeton.edu
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD020139
     1. Label: PRIDE project
     2. Name: Genetic mechanisms of cardiac sex diparities